PANK2 p.Ala427=
c.1281T>C · rs2090601871 · VCV1012473
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.47e-05%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.88 | GERP 0.75, phastCons 1 |
| Overall | ||
| CADD | 12.01 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.47e-05%
European (non-Finnish) · 1/1,180,046 alleles
Overall
6.19e-05%
1/1,614,260 alleles · very rare
exomes 1/1,461,894 · genomes 0/152,366 · joint denominator
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- PANK2
- Protein
- p.Ala427=
- Coding
- c.1281T>C
- MANE Select
- NM_001386393
- dbSNP
- rs2090601871
- Type
- single nucleotide variant
- Location
- chr20:3918745 (GRCh38)
- Gene constraint
- LOEUF 1.115 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.99 · 1 PDB
Similar variants
- PANK2 c.1082+1G>C Likely pathogenic ★★ same type
- PANK2 c.1083-1G>T Pathogenic/Likely pathogenic ★★ same type
- PANK2 c.1207-3C>G Pathogenic/Likely pathogenic ★★ same type
- PANK2 c.299-1G>A Likely pathogenic ★★ same type
- PANK2 c.905+1G>C Pathogenic ★★ same type
- PANK2 c.-21G>T Pathogenic/Likely pathogenic ★★ same type
- PANK2 p.Arg154Gln Pathogenic/Likely pathogenic ★★ same type
- PANK2 p.Arg154Trp Pathogenic/Likely pathogenic ★★ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/pank2-p-ala427 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown